A gene expression and protomi study provide further evidence for the involvement of spermidine/spermine N(1)-acetyltransferase (SSAT1) in suicide and suggests new biological determinants of suicidal behavior in bipolar disorder patients

Suicide is strongly associated with Major Affective Disorders with a risk for completed suicide 6 to 15 times higher in patients compared to the general population. Lithium is to date the most effective treatment for bipolar disorder (BD) with a well established protective effect against suicide. However, the mechanisms responsible for these clinical effects remain unclear. So far, several studies attempted to identify biological markers and genes involved in suicide. A gene expression microarray study performed using postmortem brain tissue by Sequeira et al. (2006) reported a significant reduction in expression of the gene encoding the enzyme spermidine/spermine N1-acetyltransferase 1 (SSAT1) in suicide completers with and without depression compared to controls. This result has been replicated by others. To confirm and extend these findings, we measured SSAT1 gene expression levels in lymphoblastoid cell lines (LCLs) from two populations (Sardinian, n = 41 and Canadian, n = 24) of BD subjects characterized for suicidal behaviour and healthy controls. In order to test the effect of lithium on SSAT1, each LCL was divided into two lines cultured for 7 days in media with and without LiCl (1.0 mmol/l). SSAT1 expression was significantly increased by lithium in LCLs from controls (p< 0.001) and in subjects with low (p < 0.001) and high (p < 0.001) personal and genetic risk of suicide but not in LCLs from suicide completers (p > 0.05). These findings were replicated in the Canadian sample and the analysis on the pooled dataset increased the power and the significance of our findings. In contrast with the gene expression findings the protein study showed that SSAT1 levels were significantly decreased when comparing each of the 3 groups at different risk of suicide with controls. This could suggest a compensatory effect in the pathway of polyamine system. These differences were reduced or disappeared by lithium treatment in vitro. On the other hand, no differences were shown when comparing groups with different risk of suicide either with or without lithium treatment in vitro. The proteome analysis also highlighted several proteins differentially expressed in at least one of the comparisons or according to lithium treatment. These proteins are currently being identified and results will be presented at the conference. In conclusion, our findings suggest that suicide completers might represent a distinct group of patients with an altered SSAT1 function.